Time-varying impact of established prognostic factors in resected pancreatic ductal adenocarcinoma.
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Javed Ammar A, Fatimi Asad Saulat, Rompen Ingmar F, Mahmud Omar, van Goor Iris W J M, Habib Joseph R, Andel Paul, Campbell Brady A, Schouten Thijs J, Bagante Fabio, Mughal Nabiha A, Stoop Thomas F, Lafaro Kelly J, Burkhart Richard A, Burns William R, Hewitt Brock, Sacks Greg D, van Santvoort Hjalmar C, den Dulk Marcel, Daams Freek, Mieog J Sven D, Stommel Martijn W J, Patijn Gijs A, de Hingh Ignace, Festen Sebastiaan, Nijkamp Maarten W, Klaase Joost M, Lips Daan J, Wijsman Jan H, van der Harst Erwin, Manusama Eric, van Eijck Casper H J, Koerkamp Bas Groot, Kazemier Geert, Busch Olivier R, Molenaar Izaak Quintus, Daamen Lois A, Besselink Marc G, He Jin, Wolfgang Christopher L, Dutch Pancreatic Cancer Group and the PANC-PALS Consortium
Аннотация
METHODS: This was a multicenter, retrospective cohort study of the prospectively maintained Dutch Pancreatic Cancer Recurrence Database and New York University and Johns Hopkins Hospital Institutional Databases. Patients with complete macroscopic resection of histopathologically proven PDAC between 2014 and 2019 and available follow-up data were included. The time-varying impact of prognostic factors identified by univariable Cox regression was modeled using Aalen's Additive Regression Models (Aalen's models) and visualized as plots of cumulative hazard.
RESULTS: In total, 3104 patients were included, of whom 938 (30.2%) received neoadjuvant therapy (NAT), whereas the rest underwent upfront surgery (US). A total of 201 (6.5%) patients achieved observed long-term survival (>5 years). Aalen's models showed that lymphovascular invasion, perineural invasion, and nodal disease were prognostic up to 2 years postoperatively. At varying points thereafter, these variables lost their impact in the NAT but not US patients. Similarly, during the fourth year of follow-up, American Society of Anesthesiology scores became impactful in the NAT but not in the US patients.
CONCLUSION: The impact of prognostic factors in resected PDAC across NAT and US patients is time-varying. Our results suggest that aggressive disease drives early mortality but, after NAT, tumor-biological factors lose prognostic importance to frailty and comorbidities over time.